The research proposed in this grant application is expected to be of much interest and significance to the area of drug abuse. Methione enkephalin and leucine enkephalin are endogenous peptides which appear to serve as natural ligands for opiate receptors in central and peripheral nervous systems. The two peptides are found in brain, pituitary, cerebrospinal fluid and blood. (D-Ala 2)-methione enkephalinamide and (D-phe 4)-methione enkephalin are synthetic enkephalin analogs; low doses of the former cause profound morphine-like analgesia, while the latter displays virtually no opiate activity. We propose to determine the three-dimensional molecular stereochemistry of these compounds by X-ray crystallography and compare their conformations with each other and with those of the opiate narcotics. We will obtain data that will be useful in understanding mechanisms of action at the opiate receptor site and that may be highly valuable for the design of new opiate-like but non-addictive analgesics.